Prescription opioid dependence is increasing and creates a significant public health burden, but office-based physicians lack evidence-based guidelines to decide between maintenance or detoxification treatment with buprenorphine (Bup). Although prior research has demonstrated the superiority of maintenance over detoxification for heroin dependent patients, the favorable clinical characteristics and improved treatment outcomes for prescription opioid dependent patients compared to heroin dependent patients and decreased severity of withdrawal symptoms with Bup have led many physicians to recommend detoxification with Bup for these patients. To provide data that could be used to develop evidence-based guidelines regarding detoxification or maintenance treatment for prescription opioid dependent patients, the proposed study compares Bup maintenance (Mtn) vs. detoxification (Dtx) in a 18-week randomized clinical trial of Bup in a heterogeneous population of prescription opioid dependent patients (N=120) in a primary care clinic. Patients are randomized to Mtn or Dtx after a 2-week induction period. Mtn is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services. Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Mtn, Bup will continue unchanged for the remainder of the study. In Dtx, the dosage of Bup will be tapered to zero over the next 3 weeks, and patients will not receive additional Bup for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Bup. The study will test the hypothesis that Mtn will lead to decreased illicit drug use and will demonstrate incremental cost-effectiveness compared to Dtx. Data analyses will be conducted on the intention to treat sample of randomized patients. Primary outcomes include reductions in illicit opioid use and abstinence achievement, assessed by weekly urine toxicology testing and self report. Secondary outcomes include proportion of patients protectively transferred, retention in assigned treatment, cocaine use, HIV risk behaviors, patient satisfaction and health status. Utilization and costs of services will also be evaluated. Relevance to public health: The results of this study will help define the role of maintenance vs. detoxification with buprenorphine in the care of prescription opioid dependent patients in primary care.